John Fauber, Milwaukee Journal Sentinel: August 8, 2019.
In 2011, a group of influential dermatologists, most of whom had financial ties to drug companies, issued a set of national guidelines for treating psoriasis.
It said a class of immune-suppressing drugs could be used to clear up mild skin issues before weddings or other special events.
The problem: The recommendation went against the approved uses for the drugs, which carry stringent safety warnings from the U.S. Food and Drug Administration.
In 2012, AbbVie created a “Nurse Ambassador” program that paid nurses around the country to make home visits to patients who had been prescribed Humira, its rheumatoid arthritis and psoriasis drug.
The wrinkle: The nurses were instructed not to mention the risks of the drug, which include potentially deadly infections, according to a lawsuit filed by California regulators.
In 2014, Pfizer paid for a study of its rheumatoid arthritis drug Xeljanz — one authored by 12 experts, all with financial ties to the company. Xeljanz came out on top.
The twist: It was not compared to the treatment experts consider the most effective.
All three efforts were part of a massive drug company push to boost the sale of expensive, immune-suppressing drugs to treat autoimmune conditions such as psoriasis and rheumatoid arthritis.
The drugs, many of which are biological medicines, called biologics, were introduced two decades ago and have hit $45 billion in sales, despite escalating prices and mounting reports of serious side effects.
“There are a lot of different playbooks on drugs,” said Diana Zuckerman, president of the Washington, D.C.-based National Center for Health Research, a public health advocacy group. “The industry knows how to sell a product.”
AbbVie’s nurse program is the focus of an insurance fraud lawsuit filed last year by the California Department of Insurance. It alleges the company paid kickbacks to doctors to prescribe the drug and sent the nurses into homes “to keep patients on a dangerous drug at any cost.”
The lawsuit, which claims more than $1.2 billion in insurance fraud, alleges the nurses were trained to hide Humira’s serious cancer and infection risks — allegations AbbVie denies.
The nurse program offers a unique spin on what past Milwaukee Journal Sentinel investigations have found to be a pattern of drug company money touching every step of the process.
Upbeat TV commercials and magazine ads that tout the benefits of the drugs.
Treatment guidelines that call for doctors to prescribe them — written by doctors with financial ties to drug companies.
Favorable studies underwritten by drug companies — often conducted by researchers who double as speakers and consultants to the companies.
Biologic drugs are cultured from animal cells and introduced by injection or IV.
The drugs are often effective and can lead to significant improvement in symptoms, even remission. But they also leave patients susceptible to a growing number of infections and other serious side effects.
Of the 21 biologic drugs that have won FDA approval, 13 — 62% — have received the agency’s most stringent warning, known as a “black box.” In the majority of those, the warnings were added when serious risks and side effects began showing up after the drugs were on the market.
Earlier this year, a Milwaukee Journal Sentinel investigation found more than 1 million “adverse events” were reported to the FDA in people using the drugs since 2004, including nearly 500,000 that were deemed serious.
There were 34,000 reported deaths.
While the FDA database has limitations, including a lack of verification of the reports and the possibility that other drugs could also have been used, it is the largest publicly available data set of reactions associated with prescription drugs.
If anything, experts say, it undercounts the potentially dangerous incidents.
Zuckerman, the head of the public health advocacy group, said part of the drug company strategy is to get the FDA to approve more and more products — or to get existing drugs approved to treat more and more conditions.
That creates a confused marketplace.
“The doctors are left with 20 different products and no idea which one is best for which patient,” she said.
Rising competition, rising costs
Led by top-selling Humira, biologic drugs have become some of the biggest moneymakers for the U.S. pharmaceutical industry.
Prescriptions for them were on pace to exceed more than 6 million in 2018, up from about 4 million in 2013, according to data from the pharmaceutical market research firm IQVIA. That represents a 50% increase.
Humira prescriptions were set to top 3 million, an increase of more than 60%.
Meanwhile, biologic drugs were expected to tally $45 billion in sales, with Humira on pace to hit $18 billion alone — an increase of more than 150% since 2013.
The list price on the drugs can exceed $40,000 a year, though rebates and discounts can reduce the amount paid by insurance companies and individuals.
There are now more than 20 biologic drugs on the market, in addition to other, traditional treatments for the conditions.
Yet prices seem to defy the laws of supply and demand.
A February 2019 paper in the journal JAMA Internal Medicine looked at three of the most popular biologic drugs in a class known as tumor necrosis factor inhibitors: Humira, Enbrel and Remicade.
Before 2009, they were the only such drugs approved to treat rheumatoid arthritis.
In the years that followed, the FDA approved three more drugs — increasing competition. The study authors expected costs would still rise 34% from 2009 to 2016, due to inflation and other factors. Instead, costs went up 144%.
California alleges insurance fraud
In September 2018, the California insurance commissioner’s office laid out its case of financial impropriety against AbbVie, providing a window into the push to boost sales of Humira.
A similar lawsuit was filed in federal court in Illinois.
That lawsuit alleges AbbVie officials “bragged at national sales meetings about how the Ambassador Program resurrected the otherwise plateauing sales of Humira and attributed a sharp and specific rise in sales directly to the Ambassador Program.”
Both cases are pending. AbbVie denies wrongdoing.
The California lawsuit alleges the program began as a pilot effort in 2012, developed a presence in California in 2013 and soon became “wildly successful in this state and others.”
Through the program, doctors allegedly got kickbacks in the form of cash, meals, drinks, gifts, trips, even patient referrals.
One court document indicates the national program reached 179,000 patients.
“Kickbacks and more sophisticated schemes, like those alleged in the AbbVie case, are significant drivers in the out-of-control cost of prescription drugs that harm consumers,” California Insurance Commissioner Ricardo Lara said in a statement to the Journal Sentinel.
His office estimates private insurers in California alone paid out $1.2 billion in Humira claims from 2013 to 2018, making it potentially the largest insurance fraud case in the department’s history.
Major marketing push
In 2018, Humira topped all drugs for ad spending, at $483 million, according to data from the firm Kantar Media, which tracks cross-media ad spending.
Xeljanz, a non-biologic that competes in the same market, was third at $256 million. Cosentyx, a biologic, was eighth at $180 million.
The totals include all ad spending, aside from social media, but TV commercials are clearly at the center of marketing efforts — particularly on cable news networks.
During a five-day span in mid-March, a total of 21 commercials for autoimmune system drugs — most of them biologics — were aired during cable news shows on CNN, Fox and MSNBC between 6 and 9 p.m., according to a Journal Sentinel analysis.
Rita Redberg, editor of the journal JAMA Internal Medicine, said she is struck by how many of the drugs are advertised on TV.
“It is clear (the drugs) are not selling on the merits alone, otherwise they wouldn’t need all the advertising,” said Redberg, a professor of medicine at the University of California, San Francisco.
Drug companies and treatment guidelines
Doctors frequently turn to treatment guidelines when it comes to determining how to care for patients. The guidelines, which serve as national standards for treating various diseases, often are used by front-line doctors who see patients and write prescriptions.
They are frequently issued by medical societies and related groups.
Where do the groups get their money?
Often from companies marketing the drugs.
Consider the 2011 guidelines for treating psoriasis and psoriatic arthritis issued by the American Academy of Dermatology.
Those guidelines said that if a person with a milder case of the disease has an important upcoming event, such as a wedding or graduation, it is OK to use biologic and other drugs.
However, the FDA has only approved biologic drugs for more serious cases, what is known as moderate to severe psoriasis.
The guideline-writing committee was made up of 15 experts, 12 of whom — including the chairman — had financial ties to companies that make biologic drugs.
At the time the guidelines were issued, committee chairman Alan Menter disclosed he received money from three companies that make biologic drugs for psoriasis, but did not list the amounts.
A check of the federal government’s Open Payments database showed that in 2013 he received about $90,000 from those companies. He continued to work with the companies, receiving more than $300,000 between 2014 and 2017.
Meanwhile, the American Academy of Dermatology has received millions of dollars in funding in recent years from companies that manufacture biologic drugs, based on giving levels the group lists on its website and other records. AbbVie, the maker of Humira, alone gave more than $2 million in grants and donations to the academy between 2013 and 2017.
Less expensive option not recommended
Financial conflicts were also at play in 2015 treatment guidelines for rheumatoid arthritis from the American College of Rheumatology.
Rheumatoid arthritis causes inflammation, leading to swelling, pain, stiffness and potential damage to the joints. The condition affects more than 1 million Americans.
Experts generally agree that the best first-line treatment for the condition is the generic drug methotrexate, which is normally is taken by mouth. If that fails, a biologic can be added.
But there are other options, such as adding two generic and less expensive non-biologic drugs — what is known as “triple therapy.” A 2013 paper in the New England Journal of Medicine showed that approach to be just as effective as adding the biologic Enbrel.
The effectiveness may be equal, but there is a dramatic difference in cost.
“Triple therapy” costs less than $4,000 a year, while taking a biologic drug costs about $43,000, according to an analysis provided to the Journal Sentinel by Alvaro San-Juan-Rodriguez, a research fellow at the University of Pittsburgh School of Pharmacy.
When the American College of Rheumatology issued its treatment guidelines in 2015, it did not factor in the difference in cost, which would have put biologics at a disadvantage.
The guidelines simply said either approach could be used.
Nine of the 26 members of the committee had financial relationships with companies that either made or were developing biologic drugs at the time, a Journal Sentinel analysis found.
Study ignores most effective treatment
The influence of drug company money is increasing among experts who author papers about drugs used to treat rheumatoid arthritis, according to a May 2019 paper in the journal Rheumatology.
The paper found conflicts of interest among authors in 54% of studies in 2002 and 2003. That increased to 65% for the second period examined, 2010 and 2011.
A Journal Sentinel examination of rheumatoid arthritis studies and financial disclosure forms found an especially conflicted 2014 study of the Pfizer drug Xeljanz.
All 12 authors had financial ties to the company, including eight who were employed by Pfizer, which funded the study.
What’s more, the study compared Xeljanz to the drug methotrexate alone — not the more effective treatment of methotrexate plus a low-dose steroid. The study concluded Xeljanz was better.
Other studies of rheumatoid arthritis drugs have taken the same approach.
Pfizer spokesman Steven Danehy noted the study authors are recognized experts in the field and work with many pharmaceutical companies. He added: “Further, the New England Journal of Medicine works with an editorial team that employs rigorous editorial, peer and statistical processes to evaluate manuscripts for scientific accuracy.”
Critics question why Xeljanz was tested against a “second-best treatment” — and whether patients in the trial knew what they were getting.
“Comparing the new treatment to a treatment that we already know is not good enough proves nothing,” said John Kirwan, an emeritus professor of rheumatic diseases at the University of Bristol in the U.K.
“You can’t help thinking that the company designed their study this way just to make their new treatment look good.”
Read the original article here.